Context-dependent neuronal activity in the lateral amygdala represents fear memories after extinction

The context in which fear memories are extinguished has important implications for treating human fear and anxiety disorders. Extinction of Pavlovian fear conditioning is context specific; after extinction, fear responses are reduced only in the extinction context and remain elevated in every other context. Contextual modulation of spike firing in the amygdala is a putative mechanism for the context-specific expression of extinguished fear. To test this possibility, we conditioned rats to fear two auditory conditional stimuli (CSs) and then extinguished each CS in separate and distinct contexts. Thereafter, single-unit activity in the lateral nucleus of the amygdala (LA) and freezing behavior were recorded during tests in which each CS was presented in each extinction context. Hence, each CS was tested in its own extinction context and in the context of the other CS. Conditional freezing was context dependent; fear to an extinguished CS was low in its own extinction context and high in the other test context. Similarly, the majority of LA neurons exhibited context-dependent spike firing; short-latency spike firing was greater to both CSs when they were presented outside of their own extinction context. In contrast, behavioral and neuronal responses to either non-extinguished CSs or habituated auditory stimuli were not contextually modulated. Context-dependent neuronal activity in the LA may be an important mechanism for disambiguating the meaning of fear signals, thereby enabling appropriate behavioral responses to such stimuli.